These studies will nvestigate the effects of environmental agents on the mononuclear phagocyte system (MPS). Using a panel of quantitative and objective markers of the stages of MPS activation, we will determine how environmental agents alter the activation of macrophages. We will determine if environmental agents induce activation themselves and or if they inhibit the activation produced by other stimulants. A question of particular concern will be to determine whether the activational path is altered as well as modulated. These studies further seek to determine the mechanistic bases of changes in activation produced by environmental agents, to determine whether the alterations are due to changes within or without the macrophages and to establish the specificity and importance of the changes. Finally, the studies will determine the impact of alterations in macrophages on macrophage functions of the intact host. The long range goals of these studies are to develop models of macrophage alterations produced by environmental agents and to develop rational and simple systems for analyzing and quantifying the alterations observed in these models. The ultimate goal of these studies is to determine the impact of environmental agents upon the macrophages of humans and how these effects can be ameliorated.